1. Field of Invention
The invention relates to a driving device for micro fluids and especially relates to a pneumatic driving device and the associated method for micro fluids. By the concept of recursion, a recursive pneumatic driving device and its associated method for micro fluids can be established.
2. Related Art
Because of the recent development of biochips the related technologies in the field are becoming more important ever than before, and the micro-scale total analysis system (xcexc TAS) for biochips has become the necessary key point to the design and analysis of biochips. Hence, the associated so-called micro fluid systems for biochips have become a serious research subject and are being studied extensively. The micro fluid systems let the biochips completely function and can allow the bio-chemical substances inside the biochips mix and react with the examined species entering into the biochips completely. They comprise many micro fluid elements such as micro pumps, micro valves, micro fluid pipes and micro fluid mixers. In order to integrate these micro fluid elements to become a complete micro-scale total analysis system, new and innovative structures and manufacturing processes for biochips should be further studied.
Usually the micro fluid system has to separate the incoming micro fluids into several parts, and in the mean time micro valves are conventionally utilized to separate the incoming micro fluids and to guide them into one of the following branch pipes. Micro valves are active parts and have two disadvantages when they are in use, that is, they are more expensive and their performance is not so stable. Therefore, much research has been proposed to attempt to use passive parts in constructing micro valves to overcome these disadvantages. Related research results about the micro fluid systems in the past, for example the studies of micro pumps and micro fluid switchers, are described as follows:
1. On-chip built-in mechanical micro pump: this kind of micro pump can be directly built on biochips by micro-machining technology and with this design some movable parts should be set inside the biochips. Some proposed designs based on this concept are described as follows:
First is the electrostatically driven diaphragm micro pump invented by Roland Zengerle etc., (U.S. Pat. No. 5,529,465), wherein the main body of the micro pump comprises four layers of silicon substrate. Pumping action can be accomplished by the pulsating electrostatic attraction among the upper two silicon layers induced by supplying the specific AC current (50V, 400 Hz) together with two passive check valves. The performed flow rate is about 350 xcexcl/min.
The micro machined peristaltic pump invented by Frank T. Hartley (U.S. Pat. No. 5,705,018) is a more succinct design. With this design serial flexible conductive strips are placed on the inner walls of the micro pipes of the biochips and when the electric potential pulse waves go through above the micro pipes, the serial flexible conductive strips are attracted by the electrostatic forces to move upward in sequence to form the peristaltic phenomenon of the micro pipes. Accordingly this peristaltic phenomenon can be utilized to drive the micro fluids to flow inside the micro pipes. The phase of the applied electric potential pulse waves must be carefully controlled and the peak value is about 100 V. The performed flow rate is 100 xcexcl/min.
The disadvantages of the above described on-chip built-in mechanical micro pumps are that the structures are too complicated, it is not easy to clean the micro pumps, and the manufacturing and assembling processes are difficult. These built-in mechanical micro pumps cannot be used repeatedly when they are applied to test the chemical reagents because it is very difficult to completely clean them. So, a biochip is used only one time and then discarded, but this greatly increases production cost. Unfortunately for the on-chip built-in mechanical micro pumps and the on-chip built-in peristaltic pump complicated manufacturing processes and/or costly specific materials must be utilized. Thus the production cost will be greatly increased, and of course, this result is contrary to the requirements of mass production.
In 1998 Andrews S. Dewa and Christophe J. P. Servrain proposed the design concept of remote actuators for micro fabricated fluidic devices (U.S. Pat. No. 5,788,468), wherein the active movable parts (actuators) of micro pumps are replaced on the outside surrounding regions of the biochips. Inside the biochips are placed only the on-chip movable members that are formed by LIGA technology and are similar to pistons or turbines. The actuators placed outside the biochips can drive the on-chip passive movable parts settled inside the biochips to reciprocate or to rotate in specific pump chambers to accomplish the pumping action. The focus of this proposed patent is that different precious on-chip movable parts can be easily established by LIGA technology and can be applied easily together with the associated unsophisticated chambers to achieve the pumping action for micro fluids. Hence this invention has partially overcome the problem of the high production cost of one-time-use biochips. However, the question of how power can be transmitted from the outside actuators to the on-chip movable parts was not answered.
If the outside actuators are connected with the on-chip movable parts by levers, then the movable parts cannot be completely sealed inside the pumping chambers. It is reasonable that the required engineering specifications for the production of biochips must be enhanced so that the micro fluids cannot leak out of the pumping chambers under the reciprocation of the movable parts and under the high pressure inside the pumping chambers. It was suggested in the above-described patent to utilize the magnetic rotor device to drive the movable parts sealed completely inside the pumping chambers to accomplish the pumping action by the electromagnetic effects. This suggestion was also proposed by Kaluji Tojo and Yoshiaki Hirai in 1997 for their invention xe2x80x9cmicro flow controlling pumpxe2x80x9d (U.S. Pat. No. 5,599,175). However, specific and expensive materials must be utilized to construct the magnetic pulp bodies as the movable parts.
2. On-chip built-in electrode micro pump: this kind of micro pump is not a mechanical micro pump and with this design it is not necessary to set movable parts inside the micro pump. Conventional operating principles for this kind of micro pump are classified in three different types (electroosmosis EO, electrohydrodynamics EHD and electrophorosis EP) and will be described as follows:
The invention xe2x80x9capparatus and methods for controlling fluid flow in micro channelsxe2x80x9d (U.S. Pat. No. 5,632,876) proposed by Peter J. Zanzucci etc. in 1997 is a combinative application of electroosmosis and electrohydrodynamics, wherein four electrodes classed among two pairs are interlaced inside the micro pipes of biochips. The inner pair of electrodes is set close to each other and both stretch into the micro fluids inside the micro pipes. The current circuit can be formed by this pair of electrodes and the surrounding micro fluids around this pair of electrodes when a high voltage is supplied. At the same time the surrounding micro fluids around this pair of electrodes is pushed to move along the direction against the current direction. This phenomenon is the so-called Electrohydrodynamic pumping (EHD Pumping). The other outside pair of electrodes is placed a little farther away from each other and only touch the pipe walls of the micro pipes. When hundreds to thousands of high voltages are supplied to the outside pair of electrodes, the pipe walls of the micro pipes are firstly electrically charged, then negative and positive electric charges gather on the material surfaces where the positive and negative electrodes are, respectively, and consequently when the micro fluids contain negative electric particles, these particles are attracted toward the direction to the negative electrode, which is filled with positive electric charges. The micro fluids are also attracted toward to the positive electrode, which is filled with negative electric charges. The above-described phenomenon is the so-called Electroosmosis pumping (EO pumping). The focus of this proposed invention is to combine and integrate these two different pumping phenomena with different pumping directions to accomplish the pumping actions for micro fluids and the guiding controls for micro fluids like propelling action, expelling action and stagnate action. The working micro fluids for electroosmosis must be polar solutions containing electrically charged particles, while for electrohydrodynamics they must be non-polar solutions or organic solutions. This invention claims that after the integration of these two different phenomena the methods proposed can be applied for all micro fluids whether they are polar or non-polar.
In 1997 Paul C. H. Li and D. Jed Harrison proposed another method under their thesis: transport, manipulation and reaction of biological cells on-chip using electrokinetic effects (Anal. Chem. 69,154-158), which is a combined application of electroosmosis and electrophorosis. The working principle of electrophorosis is rather simple and is described as follows: the electrical charged particles of solutions are directly attracted by electrodes and their direction of motion is against that induced by electroosmosis. However, the focus of this invention is that the electrical charged particles of solutions are attracted by both the electroosmosis and the electrophorosisto effects but the solutions are not. Therefore the principle contribution of this invention is to drive the canine erythrocytes existing inside the solutions but not the micro fluids. From the experiments it shows that the canine erythrocytes can easily be guided. Their direction of motion can be changed by the attractive force differences of the electroosmosis and the electrophorosis effects occurring among the interlaced micro pipes.
The disadvantage of the above described on-chip built-in electrode micro pumps is that there are too many restrictions for the application when in use. But from the manufacturing perspective it can be seen that the structure of the electrode micro pumps is the simplest and the production cost is lowest. However, as discussed before, there are too many restrictions for the application when in use:
The micro pipes must be filled with solutions in advance and hence it is not possible to fill examined species or reactive reagents into the empty micro pipes at first.
The EHD pump can only drive the micro fluids to move for a short time while the EO and EP pumps are mainly utilized to drive electrically charged particles of micro fluids and have no influence on the movements of micro fluids. Consequently, the pumping effect induced by the above-mentioned three micro pumps is not significant for micro fluids, and the performed flow rates are about 10 xcexcl/min. Furthermore, the driving forces of these three different micro pumps can function only in very narrow micro pipes (the diameter of the micro pipes is about 100 xcexcm) and very high voltages (hundreds to thousands of volts) must be supplied across a very short distance. Therefore, the operating cost is high.
The EHD pumps can only be applied for non-polar organic solutions while the EO and EP pumps are only adequate for polar solutions containing charged ions. The ion concentration of solutions will seriously affect the pumping efficiency of these kinds of micro pumps. Thus it is difficult to guide and control the motions of micro fluids when the incoming examined species and reactive reagents have complex compositions or the ion concentration changes in the reacting processes.
3. On-chip external servo system: this concept is the simplest way to overcome the above-mentioned problems and obviously there is no need to set active parts inside the biochips. Thus the structure of this kind of system is rather unsophisticated and the production cost is also rather low. It is also not necessary to use the micromachining technologies to construct the external servo systems and the external servo systems can be utilized repeatedly because they are not in direct contact with the examined species and reactive reagents. Thus it may be proper to utilize this kind of system to examine the reactions of biochemical substances and reagents for one-time-use biochips. However, with this design perspective another problem of the world-to-chip interface will occur, that is, the connection between the transmission pipes under ordinary scale (transmitted micro fluids may be gases or reagents) and the biochips under micro scale can only be achieved by a number of complicated micromachining technologies.
In 1998 N. J. Mourlas et al. proposed their thesis xe2x80x9cnovel interconnection and channel technologies for micro fluids, Proceedings of the xcexc TAS""98 Workshop, 1998, 27-30xe2x80x9d, in which different interconnections between transmission pipes and biochips were shown. From the design perspective of this thesis it can be clearly seen that the pressure inside the micro pipes increases rapidly when micro fluids are poured into the micro pipes or into the micro reactive chambers of biochips. Accordingly strict requirements for the connections between the transmission pipes and the biochips should be satisfied (leakage test: 60 psi, pull test: 2N). Conventional epoxy substances should be applied to enhance the connections between the transmission pipes and the biochips. From the above-described design perspective the orientation and location points of the transmission pipes should be firstly defined by DRIE technology and then the polyoxymethylene plastics are applied to form the couplers of the transmission pipes by injection modeling. Although the transmission pipes can just be inserted into biochips by the couplers, it is recommended to reheat the transmission pipes to 250xc2x0 C. in order to establish more reliable connections.
For the biochips applied to examine biochemical reactions the structures and the manufacturing processes of the on-chip built-in mechanical micro pumps are too sophisticated and their production cost is too high. For the on-chip built-in electrode micro pumps there are too many restrictions for application and their pumping efficiency is not significant. If the problem of the world-to-chip interface can be overcome with the on-chip external servo system then this would be the best way to utilize the servo systems used repeatedly as the guiding elements for micro fluids together with the biochips that are only used one time and have no active parts.
4. Pneumatic micro pump having no junctions: Dr. Yuo proposed this design, which uses simple pneumatic servo systems providing different driving gas streams with different modes. Guiding motion, expelling motion and stagnation motion of micro fluids inside the micro pipes in the internal regions of the micro reactive module can be accomplished when the driving gas stream with a specific mode flows through the airway of the micro reactive module.
5. Pressure difference driven pneumatic micro switch for micro fluids: this was proposed by Brody in 1998 and has three or more reservoirs containing pressured gas. The pressure in the junction of the reservoirs is regulated to equal that of the third pipe. The micro fluids are controlled to flow from the first channel to the second channel. The disadvantage of this design is that it is inconvenient to utilize this micro switch because all reservoirs must be connected to the air supplies independently. Pollution easily occurs if there are no fixed outward blowing gas streams when the biochips are in use.
In consideration of the above-mentioned problems the principal aim of the invention is to provide a pneumatic driving device and the associated method for micro fluids by controlling the gas flow velocities to control the flow directions of micro fluids.
A second aim of the invention is to provide a pneumatic driving device and the associated method for micro fluids that are constructed by the external servo system together with the one-time-use biochip having no active parts. A gas stream power transmission method is used to drive the micro fluids of the biochip, such that there is no need to form any connection between the external servo system and the biochip. Hence the complicated problem of the world-to-chip does not occur.
In order to achieve these objects the invention provides a pneumatic driving device and the associated method for micro fluids, which includes a pair of gas streams, an gas stream flow path structure and an gas stream flow path. The pair of the gas streams have a controllable flow rate and injection flow direction. The gas stream flow path structure formed by two gas stream inlets, a solitary gas stream fender, a gas stream flow path, a gas stream outlet, and a fluid pipe. The pair of gas streams enters the driving device at the two gas stream inlets, goes through the gas stream fender and the gas stream flow path, and flows out of the driving device at the gas stream outlet. The fluid pipe is connected with the gas stream flow path structure and the suction, the exclusion and the stagnation of one of the micro fluids inside the fluid pipe can be accomplished by adjusting the injection flow rates into the gas stream flow path structure of the pair of gas streams.
The connection between the fluid pipe and the gas stream flow path structure is formed as an outfall in the shape of an inverted triangular, a connective gas stream flow path having a big open mouth or a connective fluid pipe having a small open mouth. The form of the gas stream fender may be an arbitrary combination of a triangle, a square, a circle and a polygon. The position of the gas stream fender may be on the upper region of the outfall or near the outfall. The other end of the fluid pipe is the injection inlet for micro fluids.
The invention provides a recursive pneumatic driving device and the associated method for micro fluids. The recursive pneumatic driving device is constructed by the recursive combination of the above-mentioned inventive pneumatic driving devices. Therefore, the micro fluids inside several micro fluid pipes can be driven and controlled to separate, to mix or to change flow directions.
Further detailed technical embodiments of the invention are described together with the drawings as follows.
Further scope of applicability of the invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.